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      저자 : Qun-you Tan (검색결과 1 건)
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        Role of a Novel Pyridostigmine Bromide-Phospholipid Nanocomplex in Improving Oral Bioavailability

        Qun-you Tan,Jing-qing Zhang,Ni-ni Hu,Guo-dong Liu,Hua-feng Yin,Li Zhang,Hong Wang,Lu-yang Lu 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.3

        A novel pyridostigmine bromide (PB)-phospholipid nanocomplex (PBPLC) was prepared to increase the bioavailability of PB. A central composite design approach was employed for process optimization. The physicochemical properties of PBPLC were investigated by means of differential scanning calorimetry, ultraviolet spectroscopy, Fourier transformed infrared spectroscopy and the n-octano/water partition coefficient. The intestinal permeability of PBPLC was observed via a single pass intestinal perfusion in rats. After oral administration of PBPLC, the concentrations of PB at predetermined time points were determined by HPLC, and the pharmacokinetic parameters were computed by DAS 2.1.1 software. Multiple linear regression analysis for process optimization revealed that the optimal PBPLC was obtained when the values of X1, X2, and X3 were 8, 40oC, and 4 mg/mL, respectively. The average particle size and zeta potential of PBPLC with the optimized formulation were 204.60 nm and −25.12 mV, respectively. Non-covalent interactions between PB and phospholipids were found in the PBPLC. The n-octanol/water partition coefficient of PBPLC was substantially increased. PBPLC had better intestinal permeability in comparison with free PB. Mean plasma drug concentration-time curves of PBPLC and free PB after oral administration were both in accordance with the two-compartment open model. The values of pharmacokinetic parameters of PBPLC and free PB were the peak time (Tmax) 2 h vs 2 h, the maximum concentration (Cmax) 22.79 μg/mL vs 6.00 μg/mL, and the value of the area under the concentration vs time curve (AUC0-∞) 7128.21 μg·min/mL vs 1772.36 μg·min/mL, respectively. In conclusion, compared with free PB, PBPLC remarkably improves the oral bioavailability of PB, which is likely due to its higher lipophilicity and permeability.

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